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  • 1
    In: JAMA Cardiology, American Medical Association (AMA), Vol. 7, No. 7 ( 2022-07-01), p. 700-
    Type of Medium: Online Resource
    ISSN: 2380-6583
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 2
    In: Annals of Intensive Care, Springer Science and Business Media LLC, Vol. 7, No. S1 ( 2017-1)
    Type of Medium: Online Resource
    ISSN: 2110-5820
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2617094-2
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  • 3
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 376, No. 6594 ( 2022-05-13)
    Abstract: Although the genome is often called the blueprint of an organism, it is perhaps more accurate to describe it as a parts list composed of the various genes that may or may not be used in the different cell types of a multicellular organism. Although nearly every cell in the body has essentially the same genome, each cell type makes different use of that genome and expresses a subset of all possible genes. This has motivated efforts to characterize the molecular composition of various cell types within humans and multiple model organisms, both by transcriptional and proteomic approaches. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. RATIONALE One caveat to current approaches to make cell atlases is that individual organs are often collected at different locations, collected from different donors, and processed using different protocols. Controlled comparisons of cell types between different tissues and organs are especially difficult when donors differ in genetic background, age, environmental exposure, and epigenetic effects. To address this, we developed an approach to analyzing large numbers of organs from the same individual. RESULTS We collected multiple tissues from individual human donors and performed coordinated single-cell transcriptome analyses on live cells. The donors come from a range of ethnicities, are balanced by gender, have a mean age of 51 years, and have a variety of medical backgrounds. Tissue experts used a defined cell ontology terminology to annotate cell types consistently across the different tissues, leading to a total of 475 distinct cell types with reference transcriptome profiles. The full dataset can be explored online with the cellxgene tool. Data were collected for the bladder, blood, bone marrow, eye, fat, heart, kidney, large intestine, liver, lung, lymph node, mammary, muscle, pancreas, prostate, salivary gland, skin, small intestine, spleen, thymus, tongue, trachea, uterus, and vasculature. Fifty-nine separate specimens in total were collected, processed, and analyzed, and 483,152 cells passed quality control filtering. On a per-compartment basis, the dataset includes 264,824 immune cells, 104,148 epithelial cells, 31,691 endothelial cells, and 82,478 stromal cells. Working with live cells, as opposed to isolated nuclei, ensured that the dataset includes all mRNA transcripts within the cell, including transcripts that have been processed by the cell’s splicing machinery, thereby enabling insight into variation in alternative splicing. The Tabula Sapiens also provided an opportunity to densely and directly sample the human microbiome throughout the gastrointestinal tract. The intestines from two donors were sectioned into five regions: the duodenum, jejunum, ileum, and ascending and sigmoid colon. Each section was transected, and three to nine samples were collected from each location, followed by amplification and sequencing of the 16 S ribosomal RNA gene. CONCLUSION The Tabula Sapiens has revealed discoveries relating to shared behavior and subtle, organ-specific differences across cell types. We found T cell clones shared between organs and characterized organ-dependent hypermutation rates among B cells. Endothelial cells and macrophages are shared across tissues, often showing subtle but clear differences in gene expression. We found an unexpectedly large and diverse amount of cell type–specific RNA splice variant usage and discovered and validated many previously undefined splices. The intestinal microbiome was revealed to have nonuniform species distributions down to the 3-inch (7.62-cm) length scale. These are but a few examples of how the Tabula Sapiens represents a broadly useful reference to deeply understand and explore human biology at cellular resolution. Overview of Tabula Sapiens. Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This multimodal atlas enabled molecular characterization of more than 400 cell types.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-03-09)
    Abstract: Loss-of-function mutations in the WRN helicase gene cause Werner syndrome- a progeroid syndrome with an elevated risk of cancer and other age-associated diseases. Large numbers of single nucleotide polymorphisms have been identified in WRN . We report here the organismal, cellular, and molecular phenotypes of variant rs3087425 (c. 2500C  〉  T) that results in an arginine to cysteine substitution at residue 834 (R834C) and up to 90% reduction of WRN helicase activity. This variant is present at a high (5%) frequency in Mexico, where we identified 153 heterozygous and three homozygous individuals among 3,130 genotyped subjects. Family studies of probands identified ten additional TT homozygotes. Biochemical analysis of WRN protein purified from TT lymphoblast cell lines confirmed that the R834C substitution strongly and selectively reduces WRN helicase, but not exonuclease activity. Replication track analyses showed reduced replication fork progression in some homozygous cells following DNA replication stress. Among the thirteen TT homozygotes, we identified a previously unreported and statistically significant gender bias in favor of males (p = 0.0016), but none of the clinical findings associated with Werner syndrome. Our results indicate that WRN helicase activity alone is not rate-limiting for the development of clinical WS.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
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  • 5
    In: Intensive Care Medicine, Springer Science and Business Media LLC, Vol. 48, No. 3 ( 2022-03), p. 300-310
    Type of Medium: Online Resource
    ISSN: 0342-4642 , 1432-1238
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459201-0
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  • 6
    Online Resource
    Online Resource
    American Meteorological Society ; 2023
    In:  Bulletin of the American Meteorological Society Vol. 104, No. 9 ( 2023-09), p. S1-S10
    In: Bulletin of the American Meteorological Society, American Meteorological Society, Vol. 104, No. 9 ( 2023-09), p. S1-S10
    Abstract: —J. BLUNDEN, T. BOYER, AND E. BARTOW-GILLIES Earth’s global climate system is vast, complex, and intricately interrelated. Many areas are influenced by global-scale phenomena, including the “triple dip” La Niña conditions that prevailed in the eastern Pacific Ocean nearly continuously from mid-2020 through all of 2022; by regional phenomena such as the positive winter and summer North Atlantic Oscillation that impacted weather in parts the Northern Hemisphere and the negative Indian Ocean dipole that impacted weather in parts of the Southern Hemisphere; and by more localized systems such as high-pressure heat domes that caused extreme heat in different areas of the world. Underlying all these natural short-term variabilities are long-term climate trends due to continuous increases since the beginning of the Industrial Revolution in the atmospheric concentrations of Earth’s major greenhouse gases. In 2022, the annual global average carbon dioxide concentration in the atmosphere rose to 417.1±0.1 ppm, which is 50% greater than the pre-industrial level. Global mean tropospheric methane abundance was 165% higher than its pre-industrial level, and nitrous oxide was 24% higher. All three gases set new record-high atmospheric concentration levels in 2022. Sea-surface temperature patterns in the tropical Pacific characteristic of La Niña and attendant atmospheric patterns tend to mitigate atmospheric heat gain at the global scale, but the annual global surface temperature across land and oceans was still among the six highest in records dating as far back as the mid-1800s. It was the warmest La Niña year on record. Many areas observed record or near-record heat. Europe as a whole observed its second-warmest year on record, with sixteen individual countries observing record warmth at the national scale. Records were shattered across the continent during the summer months as heatwaves plagued the region. On 18 July, 104 stations in France broke their all-time records. One day later, England recorded a temperature of 40°C for the first time ever. China experienced its second-warmest year and warmest summer on record. In the Southern Hemisphere, the average temperature across New Zealand reached a record high for the second year in a row. While Australia’s annual temperature was slightly below the 1991–2020 average, Onslow Airport in Western Australia reached 50.7°C on 13 January, equaling Australia's highest temperature on record. While fewer in number and locations than record-high temperatures, record cold was also observed during the year. Southern Africa had its coldest August on record, with minimum temperatures as much as 5°C below normal over Angola, western Zambia, and northern Namibia. Cold outbreaks in the first half of December led to many record-low daily minimum temperature records in eastern Australia. The effects of rising temperatures and extreme heat were apparent across the Northern Hemisphere, where snow-cover extent by June 2022 was the third smallest in the 56-year record, and the seasonal duration of lake ice cover was the fourth shortest since 1980. More frequent and intense heatwaves contributed to the second-greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Glaciers in the Swiss Alps lost a record 6% of their volume. In South America, the combination of drought and heat left many central Andean glaciers snow free by mid-summer in early 2022; glacial ice has a much lower albedo than snow, leading to accelerated heating of the glacier. Across the global cryosphere, permafrost temperatures continued to reach record highs at many high-latitude and mountain locations. In the high northern latitudes, the annual surface-air temperature across the Arctic was the fifth highest in the 123-year record. The seasonal Arctic minimum sea-ice extent, typically reached in September, was the 11th-smallest in the 43-year record; however, the amount of multiyear ice—ice that survives at least one summer melt season—remaining in the Arctic continued to decline. Since 2012, the Arctic has been nearly devoid of ice more than four years old. In Antarctica, an unusually large amount of snow and ice fell over the continent in 2022 due to several landfalling atmospheric rivers, which contributed to the highest annual surface mass balance, 15% to 16% above the 1991–2020 normal, since the start of two reanalyses records dating to 1980. It was the second-warmest year on record for all five of the long-term staffed weather stations on the Antarctic Peninsula. In East Antarctica, a heatwave event led to a new all-time record-high temperature of −9.4°C—44°C above the March average—on 18 March at Dome C. This was followed by the collapse of the critically unstable Conger Ice Shelf. More than 100 daily low sea-ice extent and sea-ice area records were set in 2022, including two new all-time annual record lows in net sea-ice extent and area in February. Across the world’s oceans, global mean sea level was record high for the 11th consecutive year, reaching 101.2 mm above the 1993 average when satellite altimetry measurements began, an increase of 3.3±0.7 over 2021. Globally-averaged ocean heat content was also record high in 2022, while the global sea-surface temperature was the sixth highest on record, equal with 2018. Approximately 58% of the ocean surface experienced at least one marine heatwave in 2022. In the Bay of Plenty, New Zealand’s longest continuous marine heatwave was recorded. A total of 85 named tropical storms were observed during the Northern and Southern Hemisphere storm seasons, close to the 1991–2020 average of 87. There were three Category 5 tropical cyclones across the globe—two in the western North Pacific and one in the North Atlantic. This was the fewest Category 5 storms globally since 2017. Globally, the accumulated cyclone energy was the lowest since reliable records began in 1981. Regardless, some storms caused massive damage. In the North Atlantic, Hurricane Fiona became the most intense and most destructive tropical or post-tropical cyclone in Atlantic Canada’s history, while major Hurricane Ian killed more than 100 people and became the third costliest disaster in the United States, causing damage estimated at $113 billion U.S. dollars. In the South Indian Ocean, Tropical Cyclone Batsirai dropped 2044 mm of rain at Commerson Crater in Réunion. The storm also impacted Madagascar, where 121 fatalities were reported. As is typical, some areas around the world were notably dry in 2022 and some were notably wet. In August, record high areas of land across the globe (6.2%) were experiencing extreme drought. Overall, 29% of land experienced moderate or worse categories of drought during the year. The largest drought footprint in the contiguous United States since 2012 (63%) was observed in late October. The record-breaking megadrought of central Chile continued in its 13th consecutive year, and 80-year record-low river levels in northern Argentina and Paraguay disrupted fluvial transport. In China, the Yangtze River reached record-low values. Much of equatorial eastern Africa had five consecutive below-normal rainy seasons by the end of 2022, with some areas receiving record-low precipitation totals for the year. This ongoing 2.5-year drought is the most extensive and persistent drought event in decades, and led to crop failure, millions of livestock deaths, water scarcity, and inflated prices for staple food items. In South Asia, Pakistan received around three times its normal volume of monsoon precipitation in August, with some regions receiving up to eight times their expected monthly totals. Resulting floods affected over 30 million people, caused over 1700 fatalities, led to major crop and property losses, and was recorded as one of the world’s costliest natural disasters of all time. Near Rio de Janeiro, Brazil, Petrópolis received 530 mm in 24 hours on 15 February, about 2.5 times the monthly February average, leading to the worst disaster in the city since 1931 with over 230 fatalities. On 14–15 January, the Hunga Tonga-Hunga Ha'apai submarine volcano in the South Pacific erupted multiple times. The injection of water into the atmosphere was unprecedented in both magnitude—far exceeding any previous values in the 17-year satellite record—and altitude as it penetrated into the mesosphere. The amount of water injected into the stratosphere is estimated to be 146±5 Terragrams, or ∼10% of the total amount in the stratosphere. It may take several years for the water plume to dissipate, and it is currently unknown whether this eruption will have any long-term climate effect.
    Type of Medium: Online Resource
    ISSN: 0003-0007 , 1520-0477
    Language: Unknown
    Publisher: American Meteorological Society
    Publication Date: 2023
    detail.hit.zdb_id: 2029396-3
    detail.hit.zdb_id: 419957-1
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  • 7
    In: Implementation Science, Springer Science and Business Media LLC, Vol. 11, No. S2 ( 2016-8)
    Type of Medium: Online Resource
    ISSN: 1748-5908
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2225822-X
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Journal of Occupational & Environmental Medicine Vol. 58, No. 8 ( 2016-08), p. 747-752
    In: Journal of Occupational & Environmental Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 58, No. 8 ( 2016-08), p. 747-752
    Type of Medium: Online Resource
    ISSN: 1076-2752
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2070230-9
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  • 9
    Online Resource
    Online Resource
    American Meteorological Society ; 2022
    In:  Bulletin of the American Meteorological Society Vol. 103, No. 8 ( 2022-08), p. S11-S142
    In: Bulletin of the American Meteorological Society, American Meteorological Society, Vol. 103, No. 8 ( 2022-08), p. S11-S142
    Type of Medium: Online Resource
    ISSN: 0003-0007 , 1520-0477
    Language: Unknown
    Publisher: American Meteorological Society
    Publication Date: 2022
    detail.hit.zdb_id: 2029396-3
    detail.hit.zdb_id: 419957-1
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Journal of Mammalogy Vol. 102, No. 2 ( 2021-06-09), p. 416-427
    In: Journal of Mammalogy, Oxford University Press (OUP), Vol. 102, No. 2 ( 2021-06-09), p. 416-427
    Abstract: Adult male big brown bats (Eptesicus fuscus) sometimes occur within maternity roosts. We investigated male attendance at big brown bat maternity roosts in a Colorado study area that shows a pattern of sexual segregation by elevation. We tested multiple predictions of three nonmutually exclusive hypotheses to explain male attendance patterns: 1) sex-specific differences in energetic strategies of males and females are maintained at the lower elevation; 2) natal philopatry of inexperienced young males accounts for most attendants; 3) males gain a reproductive advantage for late summer mating at maternity roosts. We tested predictions based on captures of bats at emergence, automated monitoring of annual, seasonal, and daily roost attendance by known-age bats tagged with passive integrated transponders, and anatomical evidence for mating. Findings were most consistent with the first two hypotheses. Adult males accounted for just 3.1% of 8,192 captures of bats at 285 evening emergences from 46 roosts during 2001–2005. Daily attendance rates of males during each active season (0.10 detections/day at age 1 year and 0.20 detections/day at ≥ 2 years old) were lower than in females (0.34 at age 1 year and 0.45 at ≥ 2 years old). Only 92 of 299 males tagged as volant juveniles were detected as adults at five maternity roosts monitored 2002–2005, far fewer than female returns in every age category. We detected known-age adult males almost exclusively at their natal roosts and most males that returned (91 of 92) in years after tagging as juveniles were first detected as 1-year-olds; 20 of 21 individuals that returned at 2–4 years of age were previously detected as 1-year-olds. One-year-old males were re-encountered at annual rates 5–16 times higher than 2- to 4-year-old males, and 1-year-old males and females had lower daily attendance rates than older bats. The male reproductive advantage hypothesis was not well supported. None of 80 females examined in late summer had evidence of insemination, and not all males showed distended scrota. Daily attendance rates of tagged adult males (n = 155) and females (n = 788) were lowest during late summer, suggesting that little reproductive advantage was accrued by males utilizing maternity roosts. Attendance of male big brown bats at maternity roosts at our study area is consistent with the sex-specific energetic strategies and natal philopatry hypotheses, and mating probably occurs at higher elevation autumn roosts and hibernacula.
    Type of Medium: Online Resource
    ISSN: 0022-2372 , 1545-1542
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2066602-0
    SSG: 12
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